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Fibroblast Growth Factor 2 Modulates Hippocampal Microglia Activation in a Neuroinflammation Induced Model of Depression
Tang, Ming-ming1,2,3; Lin, Wen-juan1,2; Pan, Yu-qin1,2; Li, Ying-cong1
第一作者Tang, Ming-ming
2018-08-08
发表期刊FRONTIERS IN CELLULAR NEUROSCIENCE
通讯作者邮箱linwj@psych.ac.cn
ISSN1662-5102
卷号12页码:14
产权排序1
摘要

Recent studies indicate that disturbed structure and function of microglia can cause depression and associated neurogenesis impairments. Our previous work has demonstrated that exogenous fibroblast growth factor 2 (FGF2) reverses the depressive-like behaviors and the impaired hippocampal neurogenesis in a neuroinflammatory model of depression. However, whether and how the antidepressant effects of FGF2 involve the modulation of microglia activation has not been elucidated. In this study, to examine the effects of FGF2 on microglia activation, exogenous FGF2 was supplemented to the lateral ventricle of rats during the neuroinflammatory state induced by central lipopolysaccharides (LPS) administrations. It was found that FGF2 infusions reversed the LPS-induced depressive-like behaviors and inhibited the hippocampal microglia activation. In LPS-treated rats, FGF2 decreased the level of pro-inflammatory cytokines including interlukin-1 beta (IL-1 beta), IL-6 and tumor necrosis factor (INF)-alpha, increased the level of IL-10, the anti-inflammatory cytokine and reversed the decreased expression of CX3CL1, a chemokine mainly expressed by neurons and keeping microglia in surveillance. Further, we examined the effects of inhibited FGF2 signaling by administration of SU5402, an FGFR inhibitor. It was found that SU5402 itself evoked depressive-like behaviors, induced microglia activation, increased production of pro-inflammatory cytokines including IL-1 beta, IL-6 and TNF-alpha, and decreased the expression of CX3CL1. Two lines of results that FGF2 signaling and FGFR inhibitor can effectively but oppositely modulate the regulation of microglia and the generation of depressive-like behavior, suggesting that microglia-regulated mechanisms may underlie the antidepressant role of FGF2. The present data provide novel insights into the understanding of mechanism of neuroinflammation-associated depression and may serve as a novel mechanism-based target for the treatment of inflammation-related depression.

关键词Fibroblast Growth Factor 2 Microglia Depressive-like Behavior Neuroinflammation Cytokines Cx3cl1 Hippocampus
DOI10.3389/fncel.2018.00255
语种英语
项目资助者National Natural Science Foundation of China ; Key Laboratory of Mental Health of Chinese Academy of Sciences
资助项目National Natural Science Foundation of China[31170987] ; National Natural Science Foundation of China[31440045] ; Key Laboratory of Mental Health of Chinese Academy of Sciences[KLMH2014ZG01]
WOS研究方向Neurosciences & Neurology
WOS类目Neurosciences
WOS记录号WOS:000441076900001
出版者FRONTIERS MEDIA SA
关键词[WOS]Cell-proliferation ; Prefrontal Cortex ; Bipolar Disorder ; Brain ; Neurogenesis ; Stress ; Mice ; Inflammation ; Behaviors ; Rats
引用统计
文献类型期刊论文
条目标识符http://ir.psych.ac.cn/handle/311026/26648
专题中国科学院心理健康重点实验室
通讯作者Lin, Wen-juan
作者单位1.Inst Psychol, CAS Key Lab Mental Hlth, Beijing, Peoples R China
2.Univ Chinese Acad Sci, Dept Psychol, Beijing, Peoples R China
3.Chinese Acad Sci, Inst Zool, Beijing, Peoples R China
推荐引用方式
GB/T 7714
Tang, Ming-ming,Lin, Wen-juan,Pan, Yu-qin,et al. Fibroblast Growth Factor 2 Modulates Hippocampal Microglia Activation in a Neuroinflammation Induced Model of Depression[J]. FRONTIERS IN CELLULAR NEUROSCIENCE,2018,12:14.
APA Tang, Ming-ming,Lin, Wen-juan,Pan, Yu-qin,&Li, Ying-cong.(2018).Fibroblast Growth Factor 2 Modulates Hippocampal Microglia Activation in a Neuroinflammation Induced Model of Depression.FRONTIERS IN CELLULAR NEUROSCIENCE,12,14.
MLA Tang, Ming-ming,et al."Fibroblast Growth Factor 2 Modulates Hippocampal Microglia Activation in a Neuroinflammation Induced Model of Depression".FRONTIERS IN CELLULAR NEUROSCIENCE 12(2018):14.
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